The long-term goal of this research is to develop synthetic DNA hybridization probes to detect individuals at risk for cancer. DNA hybridization has proven highly effective as a research diagnostic tool; however, conventional DNA hybridization probes are expensive to commercialize, since they depend on enzymatically modified cloned DNA. Synthetic DNAs complementary to known sequences are relatively inexpensive to produce. These probes hybridize rapidly to specific sequences in DNA or RNA and are more sensitive to mutations and strain differences than cloned probes. Our goal is to develop an oligonucleotide-based test to detect hepatitis B virus (HBV), the integrated form of which is associated with hepatocellular carcinoma. Phase I involves the synthesis and testing of normal and modified oligonucleotides complementary to either the HBV surface antigen or core antigen genes. Phase I will compare the sensitivity and specificity of oligomer and cloned probes for filter-bound HBV sequences. Phase II will refine the use of isotopic and non-isotopic probes to detect HBV in clinical samples in order to identify individuals at risk for cancer. Once such probes are fully tested, clinical diagnositic probes for other sequences can be developed (e.g., herpes virus, Epstein-Barr virus, and viral oncogenes). (1)